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To investigate cytokeratin 19 (CK19) expression in oral squamous cell carcinoma (OSCC) tissue as well as its correlation with pathologic differentiation grade and prognosis.Cancerous and distant tissues from 33 primary OSCC patients were collected during surgery. Each sample was divided into 2 parts, one for CK19 protein detection using immunohistochemistry, and the other for CK19 mRNA-level detection of relative quantification using fluorescent real-time reverse transcriptase polymerase chain reaction (RT-PCR).The CK19 positive rate in cancerous tissue was 90.9% (30 out of 33) detected using immunohistochemistry, which was significantly higher than that in distant tissue (15.2%, 5 out of 33) by chi-square test (P < .001). The CK19 positive score in cancerous tissue was also significantly higher than that in the corresponding distant tissue by paired samples t test (P < .001). Patients with positive CK19 expression in distant tissue had higher tumor recurrence rate (P = .008) and lower survival rate (P = .015) than those with negative CK19 expression in distant tissue. Using fluorescent real-time RT-PCR, CK19 mRNA level in cancerous tissue was 2.21-fold higher than that in distant tissue (P = .020). The CK19 expression correlated significantly with pathologic differentiation grade, which was detected not only using immunohistochemistry (P = .002) but also using fluorescent real-time RT-PCR (P = .025), poorer differentiated indicating higher CK19 positive score and CK19 mRNA level.Increased CK19 protein expression and gene transcription in OSCC tissue correlate significantly with pathologic differentiation grade. Positive CK19 expression in distant tissue suggests a higher tumor recurrence rate and a lower survival rate.